The aim of these investigations is to examine the role of the dopamine (DA) system in brain in relation to the etiology, pathogenesis, and treatment of psychotic disorders. Schizophrenia and related disorders including schizophreniform disorders associated with psychotogenic drug abuse are the ultimate targets of these studies. The approach involves both pre-clinical and clinical work. In preclinical experiments the action of known and potential psychotogenic compounds upon the DA system will be studied in rats by measurement of regional concentrations of DA metabolites. In clinical work, the use of plasma catecholamine metabolites as indicators of the course of neuroleptic treatment will be pursued. The relationship between neurochemical markers of the DA system, the hypophyseal-pituitary-adrenal axis, and clinical measures of stress will be a major focus of these studies.